Loading
The trial that made an ALK pill, rather than chemotherapy, the first treatment for ALK-positive lung cancer.
Crizotinib had been approved in 2011 on single-arm response data and confirmed against second-line chemotherapy in PROFILE 1007, but whether it should come before chemotherapy was unknown. PROFILE 1014 randomised 343 patients with untreated advanced ALK-positive non-squamous disease to crizotinib 250 mg twice daily or to pemetrexed with cisplatin or carboplatin every three weeks for up to six cycles, with crossover to crizotinib permitted at progression.
Median progression-free survival by independent radiological review was 10.9 months with crizotinib against 7.0 months with chemotherapy (hazard ratio 0.45, 95 percent confidence interval 0.35 to 0.60).
PROFILE 1014 is now historical as a treatment recommendation: ALEX, ALTA-1L and CROWN each beat crizotinib with a later-generation inhibitor, and the brain, where crizotinib penetrates poorly, is where they win. Its importance is as the first demonstration that targeting the fusion beats chemotherapy from the start, the template every later fusion programme followed.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
343 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (independent radiological review)primary | Crizotinib | - | 10.9 months | 0.45 (0.35 to 0.6) | - | link |
| Pemetrexed and platinum | - | 7 months |
Shares ALTA-1L, CROWN, ALEX, Tyrosine kinase inhibitor (TKI).
Shares ALTA-1L, CROWN, ALEX, Tyrosine kinase inhibitor (TKI).
Shares Tyrosine kinase inhibitor (TKI), Oncogene addiction, Crizotinib, Gene fusion.
Shares ALTA-1L, CROWN, ALEX, ALK-positive non-small-cell lung cancer.
Shares Tyrosine kinase inhibitor (TKI), Pemetrexed, Cisplatin, Platinum agents.
Shares CROWN, Oncogene addiction, Gene fusion, ALK-positive non-small-cell lung cancer.
Shares ALEX, Alectinib, Crizotinib, ALK-positive non-small-cell lung cancer.
Shares CROWN, Crizotinib, ALK-positive non-small-cell lung cancer, ALK.